Design, synthesis, and biological evaluation of novel antimicrobials for biofilm eradication

dc.contributor.advisorChairperson, Graduate Committee: Thomas S. Livinghouse; Mary J. Cloninger (co-chair)en
dc.contributor.authorWattegedara, Isurika Buddhinien
dc.contributor.otherThis is a manuscript style paper that includes co-authored chapters.en
dc.date.accessioned2024-08-27T17:29:01Z
dc.date.accessioned2025-01-25T20:44:26Z
dc.date.available2024-08-27T17:29:01Z
dc.date.issued2024en
dc.description.abstractThe National Institutes of Health reports that biofilms account for 80% of all infections caused by microorganisms and play a substantial role in infections acquired in healthcare settings among humans. Considering the antimicrobial resistance observed toward commercially available antimicrobials, it is crucial to identify effective treatment alternatives for infections associated with biofilms. Small molecule adjuvants show promise in broadening the range of treatment options by enhancing effectiveness against both gram-positive and gram-negative bacteria. A new series of pyrimidotriazine derivatives have been synthesized as novel antimicrobial agents. Their antimicrobial efficacy was assessed against Methicillin-Resistant Staphylococcus aureus (MRSA USA300 LAC) and multidrug-resistant Pseudomonas aeruginosa (PA14) using Kirby-Bauer Disk Diffusion assays. Investigation of antibacterial screening data indicated that pyrimidotriazine compounds show higher inhibition against PA14 than MRSA at 100 mM in DMSO. An optimized synthetic route has been developed to prepare these compounds with high efficiency. Furthermore, tetrahydroimidazo[1,2-a]pyrimidinium derivatives, synthesized via the hydrogenation of imidazo[1,2-a]pyrimidinium salts, also exhibit high bioactivity against MRSA. 2-aminoimidazole heterocycle is a key pharmacophore that demonstrated its capabilities in inhibiting biofilm formation, dispersion, and resensitizes multi-drug-resistant bacterial strains to antibiotic treatments. A library of novel disubstituted 2-aminoimidazoles has been synthesized in excellent yields via an optimized route. The library was tested for the antibiofilm effect against Methicillin- resistant Staphylococcus aureus and Pseudomonas aeruginosa in Kirby-Bauer Disk Diffusion assays.en
dc.identifier.urihttps://scholarworks.montana.edu/handle/1/18782
dc.language.isoenen
dc.publisherMontana State University - Bozeman, College of Letters & Scienceen
dc.rights.holderCopyright 2024 by Isurika Buddhini Wattegedaraen
dc.subject.lcshBiofilmsen
dc.subject.lcshAnti-infective agentsen
dc.subject.lcshDrug resistanceen
dc.subject.lcshImmunological adjuvantsen
dc.subject.lcshPyrimidinesen
dc.titleDesign, synthesis, and biological evaluation of novel antimicrobials for biofilm eradicationen
dc.typeThesisen
mus.data.thumbpage38en
thesis.degree.committeemembersMembers, Graduate Committee: David M. Fialhoen
thesis.degree.departmentChemistry & Biochemistry.en
thesis.degree.genreThesisen
thesis.degree.nameMSen
thesis.format.extentfirstpage1en
thesis.format.extentlastpage126en

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